Abstract There is an unmet need for cost-efficient technologies for high purity isolation of rare circulating tumor cells (CTCs) from blood. An ideal isolation technique should be able to meet the following criteria: (a) minimal processing time; (b) low final sample volume; (c) isolation from large blood volume; (d) low carryover of leukocytes and blood components; (e) high cell viability; (f) compatibility with downstream processes such as PCR or tissue culturing; (g) low cost and ease of operation by entry-level personnel. While there are numerous approaches for CTC isolation, none of them combines simplicity, low cost, efficiency and speed. Previously, we developed a novel process of buoyant microbubble-assisted isolation of rare tumor cells from blood and buffy coats. MBs efficiently (>80% recovery) and fast (less than 20 min) isolated rare tumor cells from 7 ml blood or 22 ml buffy coats. For Phase I, Diagnologix, LLC has partnered with the University of California San Diego in order to develop and test a prototype of an intuitive and user-friendly separation/harvesting device that in combination with MBs will be used for harvesting rare tumor cells from complex biological fluids (e.g., blood). The proposed setup will enable easy washing, immunostaining, genetic analysis or culturing of isolated CTCs. The most important competitive advantages of MB approach vs. magnetic beads would be high speed, sample purity, simplicity, flexibility, minimal final sample volume and low cost. The value proposition of the technology is in the qualitative and quantitative improvement in CTC isolation and analysis for biomedical and clinical research and potentially for clinical diagnostics.